The invention is in the field of nucleic acid and polypeptide molecules associated with connective tissue diseases, progeroid disorders, and aging; methods for isolating such molecules; and the use of such molecules in human and veterinary practice.
Recently, recognition of the importance of glycosaminoglycans in animal development and human health has grown. Mutations in a human glycosaminoglycan (GAG) biosynthetic enzyme, galactosyltransferase I, may cause a progeroid variant of the connective-tissue disorder Ehlers-Danlos syndrome (EDS), a group of heritable disorders characterized by hyperelasticity of the skin and hypermobile joints.
Another GAG biosynthetic enzyme, murine EXT1, is a glycosyltransferase required for polymerization of the repeating disaccharides of heparan sulfate. Mutations in the human EXT tumor suppressor gene family are associated with a hereditary disorder, hereditary multiple exostoses (HME) that is characterized by multiple cartilaginous tumors that can be transformed to chondrosarcomas or osteosarcomas. The identification of additional mammalian genes that encode proteins that function in GAG synthesis will benefit our understanding of the role that GAG's play in human health and disease. In addition, therapeutic agents are required to modulate GAG biosynthetic pathways for the treatment of connective tissue diseases and disorders.